Department of Psychiatry, University of Texas at Austin, Austin, Texas 78712,
Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
J Neurosci. 2019 Apr 24;39(17):3264-3276. doi: 10.1523/JNEUROSCI.2713-18.2019. Epub 2019 Feb 19.
Standard fear extinction relies on the ventromedial prefrontal cortex (vmPFC) to form a new memory given the omission of threat. Using fMRI in humans, we investigated whether replacing threat with novel neutral outcomes (instead of just omitting threat) facilitates extinction by engaging the vmPFC more effectively than standard extinction. Computational modeling of associability (indexing surprise strength and dynamically modulating learning rates) characterized skin conductance responses and vmPFC activity during novelty-facilitated but not standard extinction. Subjects who showed faster within-session updating of associability during novelty-facilitated extinction also expressed better extinction retention the next day, as expressed through skin conductance responses. Finally, separable patterns of connectivity between the amygdala and ventral versus dorsal mPFC characterized retrieval of novelty-facilitated versus standard extinction memories, respectively. These results indicate that replacing threat with novel outcomes stimulates vmPFC involvement on extinction trials, leading to a more durable long-term extinction memory. Psychiatric disorders characterized be excessive fear are a major public health concern. Popular clinical treatments, such as exposure therapy, are informed by principles of Pavlovian extinction. Thus, there is motivation to optimize extinction strategies in the laboratory so as to ultimately develop more effective clinical treatments. Here, we used functional neuroimaging in humans and found that replacing (rather than just omitting) expected aversive events with novel and neutral outcomes engages the ventromedial prefrontal cortex during extinction learning. Enhanced extinction also diminished activity in threat-related networks (e.g., the insula, thalamus) during immediate extinction and a 24 h extinction retention test. This is new evidence for how behavioral protocols designed to enhance extinction affects neurocircuitry underlying the learning and retention of extinction memories.
标准的恐惧消退依赖于腹内侧前额叶皮层（vmPFC），在省略威胁的情况下形成新的记忆。我们使用 fMRI 技术在人类中研究了用新颖的中性结果替代威胁（而不仅仅是省略威胁）是否通过更有效地参与 vmPFC 来促进消退。关联的可计算建模（索引惊讶强度并动态调节学习率）描述了在新颖性促进的但不是标准的消退过程中皮肤电反应和 vmPFC 活动。在新颖性促进的消退过程中，关联的可计算性更快地更新的受试者在第二天也表现出更好的消退保留，如皮肤电反应所表达的那样。最后，杏仁核与腹侧和背侧 mPFC 之间的可分离连接模式分别描述了新颖性促进的和标准的消退记忆的检索。这些结果表明，用新颖的结果替代威胁会刺激 vmPFC 在消退试验中的参与，从而产生更持久的长期消退记忆。以过度恐惧为特征的精神障碍是一个主要的公共卫生问题。流行的临床治疗方法，如暴露疗法，是基于巴甫洛夫式消退的原则。因此，有动机在实验室中优化消退策略，以便最终开发更有效的临床治疗方法。在这里，我们使用功能神经影像学在人类中发现，用新颖的和中性的结果替代（而不仅仅是省略）预期的厌恶事件会在消退学习过程中参与腹内侧前额叶皮层。增强的消退也会减少威胁相关网络（例如，岛叶、丘脑）在即时消退和 24 小时消退保留测试中的活动。这是关于设计增强消退的行为方案如何影响消退记忆学习和保留的神经回路的新证据。
